Tinea capitis is a fungal infection of the scalp where dermatophytes in the Trichophyton and Microsporum genera invade the hair shaft and cause infection. Symptoms of tinea capitis generally present as a single or multiple patches of hair loss, sometimes with a “black dot” pattern that can be accompanied by additional symptoms such as inflammation, scaling, pustules, and itching. Trichophyton tonsurans (T. tonsurans) is one of the causes of tinea capitis, where this species of fungal infection is prevalent among school-aged children in the United States.
Tinea capitis is found to have become integrated into metropolitan communities having a striking presence and infection rate. Studies have shown that infection rates are higher than previously thought and two large scale studies of over 10,000 preschool and primary school-aged children showed schools had infection rates as high as 30%. (Abdel-Rahman, et al., Tracking Trichophyton tonsurans Through a Large Urban Child Care Center: Defining Infection Prevalence and Transmission Patterns by Molecular Strain Typing; Pediatrics, December 2006, Vol. 118, No. 6, pp. 2365-2373; Abdel-Rahman, et al.; The Prevalence of Infections With Trichophyton tonsurans in School children: the CAPITIS Study; Pediatrics; May, 2010; Vol. 125, No. 5, pp. 966-973). These studies also showed a large degree of genetic heterogeneity among the fungal isolates and a very low response rate to oral medicines administered for treatment. (Id.; Abdel-Rahman, et al., Tracking Trichophyton tonsurans Through a Large Urban Child Care Center: Defining Infection Prevalence and Transmission Patterns by Molecular Strain Typing; Pediatrics, December 2006, Vol. 118, No. 6, pp. 2365-2373; Abdel-Rahman et al., Griseofulvin has only a modest impact on eradicating carriage of Trichophyton tonsurans. Journal of Pediatric Pharmacology and Therapeutics, April 2009, Vol. 14, No. 2, pp. 94-99).
While oral medications for treating tinea capitis are known, these treatments face challenges. Often the infection is prevalent within a community of children, leading to vast opportunities for re-infection. Additionally, objects, such as bed sheets, pillows, hair brushes, stuffed toys, etc. carry the fungus and provide a means for re-infection. Objects in a classroom environment also have an impact on the prevalence of infection for the children in the classroom. Further, current oral medications used to treat tinea capitis have side effects such as liver toxicity and/or interactions with other drugs. This is in addition to the challenge presented when administering oral medication to a child, such as a child being unwilling to take a medication, ensuring enough of the medication was received, etc.
Several studies have investigated the antimycotic effect of statins, both alone and in combination with known antimycotic agents. As summarized in PCT/HU2009/000043 (the '043 application), no reference discussed therein found a generally valid antimycotic effect when using statins alone; no general synergistic antimycotic interaction between statins and known antimycotic agents can be detected; the presence or absence of a synergistic effect of statins and known antimycotic agents was different from species to species; and the fact that a combination of a statin and an antimycotic agent showed some synergistic effect does not mean that the effect could be achieved using clinically acceptable dosage ranges. The '043 application showed an additive effect for most combinations of fluvastatin and ketoconazole in Candida albicans, an additive effect for most combinations of pravastatin and miconazole in Candida glabrata, an additive effect for most combinations of simvastatin and primycin in Candida glabrata, a synergistic effect for most combinations of atorvastatin and itraconazole in Aspergillus fumigatus, an additive effect for most combinations of fluvastatin and miconazole in Aspergillus flavus, and a synergistic effect for most combinations of atorvastatin and ketoconazole in Rhizopus oryzae. However, in addition to the summary of the antimycotic effect of statins provided in the '043 application, it can be appreciated that the organisms studied in the '043 application are not dermatophytes.